A kit for predicting efficacy of immune checkpoint inhibitor on cancer patients

A technology of immune checkpoint and kit, applied in the field of immunotherapy

Active Publication Date: 2020-11-10
SUN YAT SEN UNIV CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, more and more clinical evidence shows that the expression level of PD-1 / PD-L1 and tumor mutation burden have certain limitations as biomarkers for optimal clinical decision-making of immune checkpoint inhibitor therapy.

Method used

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  • A kit for predicting efficacy of immune checkpoint inhibitor on cancer patients
  • A kit for predicting efficacy of immune checkpoint inhibitor on cancer patients
  • A kit for predicting efficacy of immune checkpoint inhibitor on cancer patients

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 The expression level of Laminin-γ2 is closely related to the efficacy of PD-1 antibody drugs

[0030] 35 patients with non-small cell lung cancer who were effectively treated with PD-1 monoclonal antibody, 36 patients with non-small cell lung cancer who were ineffective with PD-1 monoclonal antibody, and 26 patients with PD-1 Immunohistochemical staining was used to detect the expression of laminin Laminin-γ2 in the tumor tissues of 1 patient with effective monoclonal antibody therapy and 17 patients with esophageal squamous cell carcinoma PD-1 monoclonal antibody therapy ineffective. Immunostaining scoring method: staining intensity: negative = 0 points, weak expression = 1 point, moderate expression = 2 points, strong expression = 3 points; positive staining area: <25% = 1 point, 25%-50% = 2 points , 50%-75%=3 points, ≥75%=4 points; total score=staining intensity×staining area. A total score of less than 3 is considered as low expression; a total score of ≥...

Embodiment 2

[0032] Example 2 TGF-β1 promotes the expression of laminin-γ2 in tumor cells

[0033] (1) The effect of TGF-β1 concentration on the expression of laminin-γ2 in tumor cells.

[0034] Lung cancer cells (A549, purchased from ATCC, #CCL-185) and esophageal squamous cell carcinoma cells (K510, purchased from DSMZ, #ACC 374) were respectively digested with trypsin and planted on cell slides. After the cells adhered to the wall, replace The medium added with TGF-β1 recombinant protein (TGF-β1 recombinant protein concentrations were 0, 0.1, 0.5, 2.0 ng / ml), TGF-β1 recombinant protein was purchased from R&D Systems, #P01137. After 24 hours of treatment, the expression level of laminin-γ2 in cancer cells was detected by immunofluorescence staining.

[0035] The results show that: if image 3As shown in a, immunofluorescence staining shows that TGF-β1 recombinant protein can significantly stimulate the expression of laminin Laminin-γ2 in lung cancer cells (A549) and esophageal squamous...

Embodiment 3

[0043] Embodiment 3 combination therapy inhibits tumor growth

[0044] (1) Establishment of mouse subcutaneous xenograft tumor model

[0045] Twenty-six C57BL / 6 mice with sound immunity were subcutaneously injected with mouse lung cancer cells LLC (2×10 5 / only) to establish a subcutaneous xenograft tumor model, and combined therapy was carried out three weeks later.

[0046] (2) Combined therapy

[0047] Mouse PD-1 antibody was purchased from BioXcell (#BE0146), TGF-β1 receptor inhibitor Galunisertib was purchased from Selleck (#S2230), anticancer drug cisplatin was purchased from Selleck (#S1166), paclitaxel was purchased from Selleck (#S1150 ).

[0048] The subcutaneous xenograft tumor model mice obtained in step (1) were divided into 4 groups, including 5 mice in the control group and 7 mice in each drug treatment group:

[0049] Control group: injection of the same amount of sodium carboxymethylcellulose (1% CMC-Na);

[0050] Gal+anti-PD-1: Galunisertib (gastric admi...

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Abstract

The invention relates to the field of immunotherapy, in particular to a kit for predicting the curative effect of an immune checkpoint inhibitor on a cancer patient. The kit for predicting the curative effect of the immune checkpoint inhibitor on the cancer patient comprises a reagent for detecting the expression level of laminin-gamma2, and the amino acid sequence of laminin-gamma2 is shown as SEQ ID No.1. According to the invention, a new and more effective clinical marker laminin Lamin gamma2 is found to predict the curative effect of the immune checkpoint inhibitor on cancer patients, so that the cure rate of the patients is improved. Meanwhile, animal experiments find that the curative effect of the PD1 antibody can be improved by inhibiting a TGF-beta1 signal to reduce the expressionof the Laminin-gamma2.

Description

technical field [0001] The invention relates to the field of immunotherapy, in particular to a kit for predicting the curative effect of immune checkpoint inhibitors on cancer patients. Background technique [0002] Immune checkpoint therapy (immune checkpoint therapy) is a new anti-cancer immunotherapy that is currently attracting worldwide attention, leading the revolution in cancer treatment, and bringing hope to cancer patients. Its main mechanism is to block CTLA-4 and PD -1 and other signaling pathways regulate the activity of T cells to improve the anti-tumor immune response, aiming to make full use of the body's own immune system to promote the death of cancer cells. It has the potential to treat various types of tumors and substantially improve the overall survival of patients. Among them, currently, PD-1 immune checkpoint inhibitors, pembrolizumab and nivolumab have become the first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC). Ther...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68G01N33/574A61K31/444A61K39/395A61P35/00A61K33/243A61K31/337
CPCG01N33/6893G01N33/57423G01N33/57407A61K31/444A61K39/39558A61K33/243A61K31/337A61P35/00G01N2333/78A61K2300/00
Inventor 关新元李雷
Owner SUN YAT SEN UNIV CANCER CENT
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